Childhood acute lymphoblastic leukaemia (Ch-ALL)

There are a number of different types of leukaemia that affect people during childhood and early adulthood. ‘Childhood’ leukaemia is the term commonly used to describe leukaemias that are most common in younger children. However, these types of leukaemia are also diagnosed in teenagers and young adults. Although we know that teenagers and young adults have needs that are different from those of young children, the medical treatment they receive is often the same, and it is important that they are included in research to improve care for these conditions.

In the UK we normally expect to see just over 400 cases of leukaemia diagnosed each year in children under 14 years old. About 85% of these are acute lymphoblastic leukaemia (ALL) and most of the rest are acute myeloid leukaemia (AML).

Most cases of ALL in children arise in cells that would normally develop into B cells (or B lymphocytes). This is sometimes referred to as B cell ALL. A rarer form arises in cells that normally develop into T cells and is sometimes called T cell ALL. Scientists are further sub-dividing these types of ALL based on the genetic changes they see in cancer cells. Infant ALL is different from both these other forms, and is a rare and aggressive type of leukaemia that develops in babies under 12 months of age. We are supporting research into all of these leukaemias.

Our research is looking into smarter and kinder treatments, and seeking ways to improve the diagnosis and outcome and treatments for children with leukaemia. We are also supporting a project that is looking into what causes infant ALL to develop. And to find out more about how we are looking into why some children with Down’s Syndrome are more prone to developing AML, click here.

Reducing the side effects of chemotherapy

Children with ALL or a type of non-Hodgkin lymphoma called lymphoblastic lymphoma (LBL) are usually given chemotherapy made up of a number of drugs in different combinations. But chemotherapy can be harsh, particularly in children, so doctors are always looking for ways to reduce the toxicity of treatments.

We are supporting the UKALL 2011 trial, that aims to find the optimal combination of standard drugs that effectively treats ALL, but with reduced side effects.

Revolutionising the way we treat children living with ALL

Lymphoid blast cells in bone marrow usually mature into fully formed white blood cells called lymphocytes. But in ALL, the lymphoid blast cells don’t mature properly and grow too fast. These cancerous cells collect inside the bone marrow, which means there isn’t room for enough normal blood cells to be made. This is what causes most of the signs and symptoms of ALL.

There have been fantastic improvements in survival rates in the last few decades. These improvements have not been driven by new drugs, but by a greater understanding of how we can combine and dose current drugs so we can maximise their effects. But unfortunately, the life-long side effects of chemotherapy can be severe, especially in children as the drugs used and the duration of treatment can be gruelling. Not only that, if the leukaemia comes back, which it does in up to 20% of children who achieve remission, it tends to be even more difficult to treat.

Our research is looking into smarter and kinder treatments for children with leukaemia. One way will be to use therapies that specifically target the genetic faults and networks that drive cancer within the cells. This will be a significant advance on traditional chemotherapy drugs, which though they kill rapidly growing cancer cells, also damage healthy cells, causing severe side effects throughout the body.

To do this, we need to really understand what causes childhood ALL. Remarkable research funded by Bloodwise has shown that the first genetic change that leads to childhood ALL happens in the womb, but further genetic change later in childhood is needed to cause leukaemia. Understanding these steps in detail will help us take the next step forward.

Tailoring treatment to improve the outlook for children with leukaemia

Cytogenetics is the study of chromosomes, which contain tightly packed DNA. In cancer, rearrangements occur between and within chromosomes, either as the cause or as a result of the disease. Different chromosome rearrangements indicate the type of leukaemia someone has, and how they will respond to treatment.

Bloodwise has been funding The Leukaemia Research Cytogenetics Group in Newcastle University, for over 20 years. The Group has established a cytogenetics resource for acute leukaemia (ALL and AML) that is now renowned as one of the best leukaemia genetics research resources in the world.

One of their main achievements has been the development of a test that identified genetic markers in an individual’s acute lymphoblastic leukaemia (ALL), which predict the risk of relapse. This helps doctors to give the strongest treatments to those who really need it to survive, and to reduce treatment for those who will do well with less, sparing them from the harsh side effects of unnecessary treatment. This tailored approach has changed care for children with ALL, and is now used across the NHS and worldwide.

The group now want to build on this success. Using samples taken from children with leukaemia, including the rarer forms like AML, they are characterising the genetic changes with the hope of further improving the diagnosis, outcome and treatments for children with ALL.

Understanding the biology of infant ALL

Despite remarkable progress in treating childhood leukaemias, infant ALL has remained an exception to this success story. Infant ALL is biologically different to childhood ALL. This rare and aggressive type of leukaemia develops in children under 12 months of age, and in contrast to leukaemia diagnosed in older children, still has very poor survival rates, with just over half surviving for longer than five years. The chemotherapy needed is extremely harsh. Some babies die from the side effects of their treatment and many survivors suffer health problems in later life.